It is proposed to extend previous studies of TRH secretion and actions into four new areas considered to be the most relevant at present: 1) Biological, hormonal, environmental and neuropharmacological parameters will be examined to characterize systematically determinants of TRH secretion in the rat. 2) Analogous studies, where feasible, are planned in man. 3) TRH biosynthesis, sequestration, and degradation kinetics will be analyzed in rat hypothalami and extra-hypothalamic central nervous system structures in the rat in vitro. 4) Finally, potential neutrotransmitter (non-endocrine) functions of TRH will be examined at the level of the intact rat (behavioral modification), by quantitation of TRH CNS contents under a varity of biologic and neuropharmacologic modifications, and through studies of TRH inhibitory transmitter activity manifested during single neuronal recordings and TRH micro-iontophoresis. New methodologies, crucial to the projected investigations, include the capability to measure TRH, TSH in man and the rat, thyroxine, triodothyronine, and prolactin by specific, precise, and sensitive radioimmunoassays.